KFO 103:  Osteogenic Stem Cell Differentiation and Therapy of Bone Loss

• Subject Area: Medicine
• Term: from 2001 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5381915

Stimulation of bone (re)modelling and regeneration is a problem of clinical relevance. Mesenchymal stem cells are the basis for bone modelling during growth and development, and for regeneration and repair of sceletal defects in adulthood. Mesenchymal stem cells can be targets for new systemic therapeutic strategies. They may as well be expanded in vitro and prepared for local and systemic autotransplantation exploiting techniques like tissue engineering and genetic engineering. The present picture of molecular mechanisms regulating the osteogenic pathway of differentiation of mesenchymal stem cells is not complete. Master genes for osteogenic differentiation and bone metabolism encode transcription factors (e.g. cbfa1, vitamin D receptor), extracellular signalling substances (e.g. bone morphogenetic proteins, BMP, CCN-proteins (CYR61)) and integrins. This research unit will identify, characterise and produce therapy-relevant gene products which are under the control of such master genes. New findings shall influence the development and evaluation of the following issues: (1) Characterisation of new osteoinductive genes including x-ray structure analysis of signalling substances and drug design; (2) Tissue Engineering based on mesenchymal stem cell application for repair of skeletal defects; (3) Minimal invasive surgery for osteoinduction in fracture prone regions; (4) Clinical studies for therapy of local and systemic osteoporosis.

• DFG Programme: Clinical Research Units

Projects

• Die Bedeutung der Proteine der CCN-Familie für die Knochenheilung und Anwendung von Cyr61 bei Tissue Engineering zum Knochenersatz (Applicant Schütze, Norbert )
• Die sezernierten Phosphatonine FGF23 und sFRP4 - ihre Bedeutung bei der osteogenen Differenzierung, im Phosphatstoffwechsel und ihr therapeutisches Potential für das Tissue Engineering (Applicant Jakob, Franz )
• Humane mesenchymale Stammzellen - Charakterisierung, osteogene Differenzierung und Implikationen für Tissue Engineering des Knochen (Applicant Nöth, Ulrich )
• Leitung, Organisation, Symposien etc. (Applicant Eulert, Jochen )
• Physiologische BMP Signale in osteogenen Stammzellen: Liganden, Rezeptorketten, Modulatoren und Signalproteine (Applicant Sebald, Walter )
• Service Biomechanik und Histomorphometrie (Applicant Duda, Georg )

• Spokesperson: Professor Dr. Jochen Eulert
• Leader: Professor Dr. Franz Jakob